Unlocking Therapeutic Potential of Novel Thieno-Oxazepine Hybrids as Multi-Target Inhibitors of AChE/BChE and Evaluation Against Alzheimer's Disease: In Vivo, In Vitro, Histopathological, and Docking Studies.

Alzheimer's disease (AD) is largely linked with oxidative stress, the accumulation of amyloid- plaques, and hyperphosphorylated -protein aggregation. Alterations in dopaminergic and serotonergic neurotransmission have also been implicated in various AD-related symptoms. : To explore new therapeutic agents, a series of bicyclic and tricyclic thieno-oxazepine derivatives were synthesized as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors.

Novel Pyrrolidine-bearing quinoxaline inhibitors of DNA Gyrase, RNA polymerase and spike glycoprotein.

Anti-infective agents are a class of drugs used to prevent, treat, or control infections caused by microorganisms such as bacteria, viruses, fungi, and parasites. They play a crucial role in modern medicine, helping to reduce the severity of infections and, in many cases, save lives. This study aims at the design and synthesis of hybrid compounds containing quinoxaline, pyrrolidine, and an azo bridge to combat antimicrobial resistance, and evaluating their antimicrobial, antifungal, and antiviral activities against various pathogenic strains.

Discovery of novel bicyclic and tricyclic cyclohepta[b]thiophene derivatives as multipotent AChE and BChE inhibitors, in-Vivo and in-Vitro assays, ADMET and molecular docking simulation.

Alzheimer's disease (AD) is primarily caused by oxidative stress, hyperphosphorylated τ-protein aggregation, and amyloid-β deposition. Changes in dopaminergic and serotoninergic neurotransmitter pathways are linked to certain symptoms of AD. Derivatives of bicyclic and tricyclic cyclohepta[b]thiophene were developed to identify new potential candidates as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors for the treatment of AD.

Exploring a novel thiazole derivatives hybrid with fluorinated-indenoquinoxaline as dual inhibitors targeting VEGFR2/AKT and apoptosis inducers against hepatocellular carcinoma with docking simulation.

Hepatocellular carcinoma (HCC) ranks as the third most prevalent reason for cancer-related death on a global scale. Tyrosine kinase inhibitors (TKIs) continue to be the primary treatment option for advanced hepatocellular carcinoma. A series of fluoro-11H-indeno[1,2-b]quinoxaline derivatives as an HCC drug targeting the VEGFR2/AKT axis was designed and synthesized.

The role of current synthetic and possible plant and marine phytochemical compounds in the treatment of acne.

Acne is a long-standing skin condition characterized by plugged hair follicles due to the accumulation of dead skin cells, sebum, and () bacteria, causing inflammation, and the formation of pimples or lesions. Acne was recognized in the ancient times by the ancient Egyptians, Greeks, and Romans. Since ancient times, folk medicine from different cultures have comprised herbal and natural products for the treatment of acne.

Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting -amylase, and -glucosidase: synthesis, molecular docking, and ADMET studies.

Inhibition of α-glucosidase and -amylase are key tactics for managing blood glucose levels. Currently, stronger, and more accessible inhibitors are needed to treat diabetes. Indeno[1,2-] quinoxalines-carrying thiazole hybrids were created and described using NMR.

Erratum to "Facile synthesis and in anticancer evaluation of a new series of tetrahydroquinoline" [Heliyon 7(10) (October 2021) e08117].

[This corrects the article DOI: 10.1016/j.heliyon.

Interception of Epoxide ring to quorum sensing system in Enterococcus faecalis and Staphylococcus aureus.

Quorum sensing inhibitor (QSI) has been attracting attention as anti-virulence agent which disarms pathogens of their virulence rather than killing them. QSI marking cyclic peptide-mediated QS in Gram-positive bacteria is an effective tool to overcome the crisis of antibiotic-dependent chemotherapy due to the emergence of drug resistance strain, e.g.

Development of new spiro[1,3]dithiine-4,11'-indeno[1,2-b]quinoxaline derivatives as S. aureus Sortase A inhibitors and radiosterilization with molecular modeling simulation.

Multi-drug resistant microbes have become a severe threat to human health and arise a worldwide concern. A total of fifteen spiro-1,3-dithiinoindenoquinoxaline derivatives 2-7 were synthesized and evaluated for their biological activities against five standard and MDRB pathogens. The MIC and MBC/MFC for the most active derivatives were determined in vitro via broth microdilution assay.

The effect of novel synthetic semicarbazone- and thiosemicarbazone-linked 1,2,3-triazoles on the apoptotic markers, VEGFR-2, and cell cycle of myeloid leukemia.

Vascular Endothelial Growth Factor II (VEGFR-2) has been proved as a rational target in cancer therapy. Although currently prescribed VEGFR-2 inhibitors are showing potent antitumor activity, they are often causing serious unwanted effects, restricting their extensive use as chemotherapeutics. Herein, after analyzing the structures of the effective VEGFR-2 inhibitor molecules, we report the synthesis of a new set of semicarbazone- and thiosemicarbazone-linked 1,2,3-triazoles with expected potency of inhibiting the VEGFR-2 signaling.

Apoptosis induction, PARP-1 inhibition, and cell cycle analysis of leukemia cancer cells treated with novel synthetic 1,2,3-triazole-chalcone conjugates.

Leukemia is a life-threatening nonepithelial malignant disorder that is characterized by uncontrolled growth of the hematopoietic cells. To date, there are still unmet needs for effective and less toxic medication for the management of this malignant tumor. Here, we report the synthesis of a new set of suggested anticancer molecules by joining the 1,2,3-triazole and chalcone privileged fragments in one scaffold to develop novel candidates in leukemia therapy.

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein.

The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19.

Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study.

Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In and , regulation of virulence genes' expression occurs through the cyclic peptide-mediated accessory gene regulator () and its ortholog quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria.

Upregulation of BAX and caspase-3, as well as downregulation of Bcl-2 during treatment with indeno[1,2-b]quinoxalin derivatives, mediated apoptosis in human cancer cells.

Cancer is the world's foremost cause of death. There are over 100 different forms of cancer. Cancers are frequently named after the organs or tissues in which they develop.

Facile synthesis and anticancer evaluation of a new series of tetrahydroquinoline.

Tetrahydroquinoline () is an important structure for synthesizing multiple biologically active derivatives. Thus, we developed new quinoline derivatives and investigated them as anticancer agents. First, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and other techniques were used to confirm the structure of synthesized compounds.

Hydrazonoyl bromide precursors as DHFR inhibitors for the synthesis of bis-thiazolyl pyrazole derivatives; antimicrobial activities, antibiofilm, and drug combination studies against MRSA.

Microbial resistance is a big concern worldwide, making the development of new antimicrobial drugs difficult. The thiazole and pyrazole rings are important heterocyclic compounds utilized to produce a variety of antimicrobial medications. As a result, a series of new bis-thiazolyl-pyrazole derivatives 3, 4a-c, 5a, b, and 6a-c was synthesized by reacting bis hydrazonoyl bromide with several active methylene reagents in a one-pot reaction.

In vivo screening and toxicity studies of indolinone incorporated thiosemicarbazone, thiazole and piperidinosulfonyl moieties as anticonvulsant agents.

Based on the biological importance of the thiazole nucleus, we decided to prepare and evaluate the biological activity of some new isatin derivatives containing thiazole moiety. The 5-(piperidin-1-ylsulfonyl)indoline-2,3-dione (1) was prepared and used as a starting material in the synthesis of many isatin derivatives for anticonvulsant evaluation. All the newly synthesized thiazlidino/thiosemicarbazide-indolin-2-one derivatives screened in vivo for their anticonvulsant activity against pentylenetetrazole-induced convulsions in mice.

In vitro antimicrobial evaluation and in silico studies of coumarin derivatives tagged with pyrano-pyridine and pyrano-pyrimidine moieties as DNA gyrase inhibitors.

Several coumarin-containing substitute nitrogen heterocycles have recently received considerable importance due to their diverse pharmacological properties. One-pot and rapid synthesis of coumarin derivatives was achieved via reactions of acetyl-coumarin with p-chloro-benzaldehyde and malononitrile to provide compound 2-containing cyano-amine using conventional heating. Compound 2 was condensed with different carbon electrophiles triethyl orthoformate, phenyl isocyanate, carbon disulfide, benzoyl chloride, and acetyl chloride that afforded the corresponding chromene derivatives 3-17.

Novel structural hybrids of quinoline and thiazole moieties: Synthesis and evaluation of antibacterial and antifungal activities with molecular modeling studies.

One of the best ways to design new biocidal agents is synthesizing hybrid molecules by combining two or more bioactive moieties in a single molecular scaffold. So, new series of quinolines bearing a thiazole moiety were synthesized using thiosemicarbazones 2a-f. Cyclization of 2a-f with ethyl chloroacetate, ethyl 2-chloropropanoate or chloroacetone afforded the corresponding thiazoles 3-5.

In vivo and in vitro anti-inflammatory, antipyretic and ulcerogenic activities of pyridone and chromenopyridone derivatives, physicochemical and pharmacokinetic studies.

Throughout this study, we present the victorious synthesis of a novel class of 2(1H)-pyridone molecules, bearing a 4-hydroxyphenyl moiety through a one-pot reaction of 2-cyano-N-(4-hydroxyphenyl)acetamide with cyanoacetamide, acetylacetone or ethyl acetoacetate, and their corresponding aldehydes. In addition, the chromene moiety was introduced into the pyridine skeleton through the cyclization of the cyanoacetamide 2 with salicylaldehyde, followed by treatment with malononitrile, ethyl cyanoacetate, and cyanoacetamide, in order to improve their biological behaviour. Due to their anti-inflammatory, ulcerogenic, and antipyretic characters, the target molecules have undergone in-vitro and in-vivo examination, that display promising results.

In vitro cytotoxic activity of thiazole-indenoquinoxaline hybrids as apoptotic agents, design, synthesis, physicochemical and pharmacokinetic studies.

In this study, anti-proliferative effects of twenty-seven indeno[1,2-b]quinoxalin-11-one derivatives were investigated in three human cancer cell lines, namely: the colon cancer cell line HCT-116, the liver cancer cell line HepG-2, and the breast cancer cell line MCF-7. Among them, 5, 6, 13, 14a, b and 15d-f derivatives displayed excellent anti-proliferative activities against the three tested cell lines compared to the reference standard Imatinib. Therefore, they were selected for further studies.

Antimicrobial evaluation of thiadiazino and thiazolo quinoxaline hybrids as potential DNA gyrase inhibitors; design, synthesis, characterization and morphological studies.

A series of thiadiazino[5,6-b]quinoxaline and thiazolo[4,5-b]quinoxaline derivatives was designed and synthetized from the reaction of 2,3-dichloro-6-(morpholinosulfonyl)quinoxaline (2) with thiosemicarbazide or thiocarbohydrazide and thiourea derivatives to give nineteen quinoxaline derivatives 3-16. All the synthesized compounds were evaluated for in vitro antimicrobial potential against various bacteria and fungi strains that showed considerable antimicrobial activity against tested microorganisms. The most potent compounds 2, 7, 9, 10, 12 and 13c were exhibited bactericidal activity, in addition to fungistatic activity by dead live assay.

Electrode impedance changes over time in MED El cochlear implant children recipients: Relation to stimulation levels and behavioral measures.

Electrode impedance measures resistance encountered by electric current passing through wires, electrodes and biological tissue. This study was designed mainly to evaluate changes in electrode impedance values and psycho-electric parameters changes (i.e.

Design, synthesis, cytotoxicity and molecular modeling studies of some novel fluorinated pyrazole-based heterocycles as anticancer and apoptosis-inducing agents.

3,5-Diamino-4-(3-trifluoromethylphenyldiazenyl)-1H-pyrazole was used as a starting scaffold for the synthesis of new pyrazole-based heterocycles to study their effects on the proliferation of three human cancer cell lines; human liver carcinoma cell line (HepG-2), colon cancer cell line (HCT-116) and human breast cancer cell line (MCF-7) using MTT assay. The synthesized compounds were characterized on the basis of IR, H NMR, C NMR, mass spectral data and elemental analysis results. Cytotoxicity assay results revealed that some of the compounds showed potent growth inhibition against all the cell lines tested, with IC50 values in the range of 0.

Quinoline derivatives bearing pyrazole moiety: Synthesis and biological evaluation as possible antibacterial and antifungal agents.

In an attempt for development of new antimicrobial agents, three series of quinoline derivatives bearing pyrazole moiety have been synthesized. The first series was synthesized through the synthesis of 4-(quinolin-2-yloxy)benzaldehyde and 4-(quinolin-2-yloxy)acetophenone and then treatment with ketone or aldehyde derivatives to afford the corresponding chalcones. Cyclization of the latter chalcones with hydrazine derivatives led to the formation of new pyrazoline derivatives.